The present invention relates generally to analgesic compositions and methods for administering these compositions and more particularly to analgesic compositions comprising myfadol and to methods for administering these compositions orally.
Analgesic compositions are pain relieving agents. Familiar analgesic compositions are aspirin and ibuprofin, both of which are non-steroidal antiinflammatory drugs (NSAID). A problem with NSAID-type analgesic compositions is that they have a plateau effect: they do a good job of relieving relatively mild levels of pain, but they are not good at relieving relatively severe levels of pain. Relief from severe levels of pain often requires the use of opioids.
Opioid analgesic compositions are narcotic compositions, and they have drawbacks. Tolerance and addiction can develop after repeated use. In addition, opioid analgesic compositions are capable of producing respiratory depression, excessive sedation, and, on occasion, cardio-vascular depression.
It would be desireable to provide an analgesic composition which has the pain-relieving properties of opioid analgesic compositions but without the drawbacks which accompany their use. It would be most desireable to produce an analgesic composition having the properties described in the preceding sentence and which can be readily administered orally.
The analgesic composition, myfadol, has been administered by injection, both intravenously and intramuscularly. It has pain relieving properties comparable to those of opioid analgesic compositions, yet it produces less undesired side effects than opioid analgesic compositions. There is a report on tests conducted with myfadol administered by injection to humans; the report is in Shulman et al.: Studies With Myfadol, A New Analgesic Agent. Anesthesia And Analgesia . . . Current Researches, Vol. 49, No. 6, November-December 1970, p. 905; and the disclosure therein is incorporated herein by reference. The Shulman publication reports on the efficacy and side effects produced by various dosages of myfadol, expressed as milligrams of myfadol per kilogram of human patient body weight. From the standpoint of both efficacy and side effects, a dosage of 1.0 mg/kg was found to be superior to both 0.5 and 1.5 mg/kg. The Shulman publication concludes (at page 910) that single intravenous dosages of myfadol should not exceed 1 mg/kg.
When one desires to introduce orally an analgesic composition that has previously been introduced by injection, it is generally necessary to employ larger dosages of the analgesic composition. This is due to the so-called "first pass" effect produced by the liver which metabolizes an orally administered dosage of an analgesic composition and renders it ineffective up to a certain maximum amount. Anything over that amount is significantly effective. The "first pass" effect also eliminates side effects for all analgesic dosages up to the maximum amount of oral dosage which is ineffective.
Generally, one can tolerate an oral dosage that is 2-3 times greater than the maximum amount employed when administration is by injection, without producing undesireable side effects, while at the same time obtaining a significant pain-relieving effect. However, when myfadol was administered orally in those amounts (i.e. 2-3 mg/kg of human patient body weight), there was no significant pain relief.